Biologics Show Big Promise in Restoring Sense of Smell in CRSwNP, Meta-Analysis Finds
Denmark: A new systematic review and meta-analysis has shed light on how effectively biologic therapies can help restore the sense of smell in adults living with chronic rhinosinusitis with nasal polyps (CRSwNP)—one of the most distressing symptoms of the condition.
The study, led by Christian K. Pedersen from the University of Copenhagen, evaluated the performance of several biologic agents and found that while most delivered meaningful improvements, dupilumab demonstrated the strongest overall benefit.
The analysis, published in Current Allergy and Asthma Reports, brings together evidence from 28 studies, including eight randomized controlled trials (RCTs) involving 2,024 participants and 20 observational cohort studies with an additional 1,685 patients. The researchers examined six biologic drugs assessed in RCTs: dupilumab, omalizumab, mepolizumab, benralizumab, tezepelumab, and telikibart. Their primary focus was the change in olfactory performance measured using validated psychophysical tests, such as the University of Pennsylvania Smell Identification Test (UPSIT).
Key findings of the meta-analysis were as follows:
- Biologics collectively had a moderate-to-large positive impact on smell recovery across trials.
- The pooled standardized mean difference (SMD) for improvement in olfactory scores was 0.72, indicating a statistically significant treatment effect.
- In studies that reported UPSIT outcomes, patients receiving biologics showed an average improvement of 7.37 points, reflecting a meaningful enhancement in quality of life.
- Dupilumab produced the most notable improvement among all biologics reviewed, with an SMD of 1.16 across four RCTs.
- Benralizumab also showed substantial benefit, achieving an SMD of 1.03, though this was based on a single trial.
- Tezepelumab and telikibart demonstrated modest but meaningful improvements in olfactory scores.
- Omalizumab showed a smaller yet statistically significant improvement in smell function.
- Mepolizumab did not demonstrate a significant benefit in restoring smell, although the limited data prevented firm conclusions.
- Treatment response was associated with patients’ blood eosinophil levels, indicating that biologics may be more effective in individuals with higher eosinophil counts.
- These results support the potential role of biomarker-driven approaches to personalize biologic therapy and optimize patient outcomes.
The cohort studies included in the analysis aligned closely with the RCT findings, again highlighting strong improvements—particularly among patients treated with dupilumab.
The authors emphasized the clinical importance of these results, noting that smell loss significantly impacts daily functioning, safety, and overall well-being. “The restoration of olfaction should be recognized as a central outcome of biologic therapy in CRSwNP patients and integrated into both clinical practice and guideline development,” they wrote.
Overall, the evidence suggests that biologics—especially dupilumab—offer substantial benefit in restoring olfactory function in patients with severe CRSwNP. As newer agents continue to emerge, the researchers call for direct head-to-head trials to better understand how these therapies compare and to refine treatment selection for patients who stand to benefit the most.
Reference:
Pedersen, C.K., Backer, V., Tidemandsen, J.E. et al. Restoring the Sense of Smell: A Systematic Review and Meta-Analysis of Biologic Therapies for Chronic Rhinosinusitis with Nasal Polyps. Curr Allergy Asthma Rep 25, 54 (2025). https://doi.org/10.1007/s11882-025-01235-4
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